SBIR-STTR Award

A tailored polymer matrix as made representative of the partially expanded inferior conjunctival sac will provide far better controlled drug dose delivery than contact lenses or eye drops, and will minimize the expulsion and discomfort problems of previous ocular insert products for the treatment of chronic glaucoma. This larger yet more comfortable design could retain a larger reservoir of the glaucoma drug, timolol, contact a larger tissue area, and be worn effectively for extended periods measured in weeks or months rather than hours or days. This would reduce the significant problems of noncompliance and side effects of conventional eye drop therapy for the treatment of glaucoma. The specific aims of Phase I of the proposed research are to: 1. Cast four representative polypropylene glycol containing polymeric networks of varying hydrophobicity. 2. Characterize the prepared polymer matrices with respect to hydrophilic/hydrophobic nature via solvent swell measurements. 3. Determine the release kinetics of timolol maleate from the four prepared polymeric matrices into buffer solution 4. Define a prototype design for a polymeric insert of the human inferior conjunctival sac

Using a unique polymer matrix, tailored to the chemistry of the drug, timolol, and molded into an ocular insert in a design compatible with the conjunctival sac, we will affect the release of drug for the treatment of glaucoma over a 30 to 90 day period. Customizing a matrix with such specific chemistry is an innovative approach to ocular inserts. The long duration of release at constant rates achieved via this approach, as evidenced by Phase I in vitro results, represents a significant advance in the field and will have implications on efforts at many companies and institutions working towards extended release of drugs in ophthalmology. In Phase II we intend to show feasibility of the insert design in humans, as well as measure drug release rates in an animal model. Concurrently, we will develop a molding process similar to that used in contact lens manufacture. Efforts will be coordinated in three key fields: material development and chemistry, design and process engineering and clinical/biological studies. The specific aims are:1. Produce ocular insert material containing 1.0 percent to 5.0 percent timolol and determine the release kinetics over this concentration range from test samples.2. Develop a cast molding, photopolymerization process and produce "small" and "medium" size inserts.3. Demonstrate the safety of the ocular insert material (non-drug loaded) utilizing both in vitro and in vivo testing.4. Determine the comfort and stability of the ocular insert (non-drug loaded) in a selected patient clinical study utilizing both the "small" and "medium" size inserts.5. Determine the in vivo release characteristics of the timolol-containing ocular insert in the rabbit model.6. Develop a business plan that will be presented to potential corporate partners to secure Phase Il funding